The rates of major depressive disorder (MDD) among women who have recently experienced perinatal loss (including early and late fetal death and early neonatal death) are 3 times the rates of MDD among matched samples of community women. Mood difficulties can persist up to 4 years after the loss and can worsen with subsequent pregnancies. Suicide rates after perinatal loss are higher relative to mothers of living infants. PTSD is a common co-occurrence; PTSD rates after perinatal loss are 7 times that of mothers of living infants. Despite recognition that MDD following perinatal loss is an important public health concern, that it causes significant impairment, and that treatment as usual has been inadequate, the only treatment developed and tested for this population was part of a randomized trial conducted by our team in pilot work for this proposal. That study created the first manual for treating any psychiatric disorder after perinatal loss. The manual is structured, easy-to-follow, and uses interpersonal psychotherapy (IPT) principles to address the circumstances perinatal loss, such as resolving conflicts over how to respond to the loss, grieving and requesting support in the absence of social norms about how to do so, reviewing the loss event, and resolving questions of fault and role competence. It can be used by providers who do not know IPT. Our pilot trial randomized 50 women with MDD following perinatal loss to group IPT or to group Coping with Depression (CWD), an evidence-based cognitive behavioral treatment which did not focus on perinatal loss nor social support. IPT was feasible and acceptable, with significantly higher (p = .001) treatment satisfaction scores and PTSD recovery rates (among the 54% of the sample with PTSD; p = .009) in IPT than in CWD. Confidence intervals around between-groups effect sizes favored IPT for reductions in depressive symptoms during treatment as well as for improvement in mode-specific targets (social support, grief symptoms), over follow-up. Given these promising findings, the proposed R01 will conduct a fully-powered randomized efficacy study comparing IPT for MDD following perinatal loss to CWD in a sample of 274 women. The trial will be the first fully-powered randomized trial of treatment for any psychiatric disorder following perinatal loss. It addresses NICHD priority to improve the health of women before, during, and after pregnancy. Given that poverty increases risk of perinatal loss and that rates of perinatal loss for African- American women are double those for White women, the location of the trial in Flint and Detroit, Michigan (minority-majority cities with high rates of poverty) increases the significance of the trial. Outcomes will include time to recovery from MDD, depressive symptoms, PTSD symptoms, time to recovery from PTSD, social support, well-being, grief, and fear of subsequent pregnancies. Results have high potential for dissemination and uptake: we have received and fulfilled more than 160 requests for the free, unpublished IPT treatment manual. This study will provide an evidence base for treating a vulnerable and understudied population whose distress has historically been minimized, improving outcomes for these women and their families.